This Program Project is founded on the premise that AGING is a natural process and that many changes occur as an extension of normal development. We have been testing this thesis by chemically characterizing the PROTEOGLYCANS synthesized by non-cartilage tissue as a function of age, starting with very early development through adulthood and in aged subjects. We base this exploration on our considerable experience in the characterization of cartilage proteoglycans where in chick embryonic, bovine, sheep, and human cartilages, we and others have been able to show that there is an age-dependent, programmatically controlled changing pattern of proteoglycan biosynthesis. The sources of the proteoglycans for the individual projects described here are chick or CBF-1 mouse muscle, aging human fibroblast cell lines and primary isolates of skin fibroblasts from human subjects scored for genetic history, chronological age and "apparent skin age". Detailed chemical, physical chemical, and electron microscopic analyses of purified proteoglycans during early development, adulthood, and senescent stages are being conducted. We are focusing on the proteoglycans in the extracellular matrix both closely associated with the cells (surface adhesion material) and in the space between cells. By analyzing the newly synthesized material, we hope to be able to describe the programmatically controlled biosynthesis of proteoglycans as well as gain insight into various organizational and interactive properties of these complex macromolecules. A goal of these descriptive explorations is to attempt to relate the chemical and physical chemical properties of proteoglycans with age-related changes of the tissues from which the cells originated. Such a detailed characterization of proteoglycan biosynthesis, structure, cytological localization, and function should allow us to comment on the validity of the thesis of "the ontogenetic basis of aging."